Nociception opioid receptor role

Dynorphin may also influence nociception at the spinal level. The levels of prodynorphin mRNA and immunoreactive dynorphin increase in the chronic inflammatory arthritic model (158). Dynorphin also inhibits morphine or P-endorphin-induced analgesia in naive animals and enhances analgesia in tolerant animals, indicating that this peptide may have a regulatory role in opioid analgesia (159). This effect does not appear to be mediated by a classical opioid receptor, since des-tyrosine dynorphin, which does not bind to opioid receptors, also antagonizes morphine analgesia (160). 

In contrast to the analgesic role of leu- and met-enkephalin, an analgesic action of dynorphin A—through its binding to (kappa) opioid receptors—remains controversial. Dynorphin A is also found in the dorsal horn of the spinal cord, where it may play a critical role in the sensitization of nociceptive neurotransmission. Increased levels of dynorphin can be found in the dorsal horn after tissue injury and inflammation. This elevated dynorphin level is proposed to increase pain and induce a state of long-lasting hyperalgesia. The pronociceptive action of dynorphin in the spinal cord appears to be independent of the opioid receptor system but dependent on the activation of the bradykinin receptor. Moreover, dynorphin A can bind and activate the N -methyl-D-aspartate (NMDA) receptor complex, a site of action that is the focus of intense therapeutic development. 

Fleetwood-Walker, S. M., Mitchell, R., Hope, P. J., El-Yassir, N., Molony, V. The roles of tachykinin and opioid receptor types in nociceptive and non-nociceptive processing in superficial dorsal horn. In Fine afferent nerve fibers and pain, 1987, edited by R. F. Schmidt, H. G. Schaible, C. Vahle-Hinz, 239-247, VCH, Weinheim. 

A consensus of different studies appears to be that the spinal dynorphin system plays an inhibitory role in nociceptive transmission mediated through the K-opioid receptor in an acute pain state, and a facilitative role mediated through an NMDA receptor mechanism in a chronic pain state when the K-opioid receptor became tolerant due to sustained activation by endogenous dynorphins (Xu et al., 2004). Our studies suggest that the prodynorphin system also has a pronociceptive function in normal uninjured animals. 

Endogenous opioids and their multiple receptors continue as the focus of vigorous research. The proceedings of the 1983 International Narcotic Research Conference were published, and reviews were recently provided on opioid peptides,opioid receptors and their functional roles,pharmacology and therapeutic implications of enkephalins and endorphins, " cardiovascular effects of endogenous opioids, opioids and the adrenal-pituitary axis, opioids and the hippocampus, substance P in nociception, potential therapeutic roles for opioid antagonists, roles of opioid peptides in appetite control,and autoradiography of opioid receptors. 

According to the NC-IUPHAR Subcommittee on Opioid Receptois it was proposed to term ORL-1 recqrtor as NOP receptor [1]. The human NOP receptor gene encodes a protein of370 amino acids. Splice valiants have been found in the human and mouse NOP recqrtor with no known functional significance. NOP receptors are widely distributed throughout the brain and in the spinal cord. They are also present in immune cells. A functional role for N/OFQ has been proposed in nociception, locomotoric activity, reward, stress, and immunomodulation. 

Sierra V, Duttaroy A, Lutfy K, Candido J, Billings B, Zito SW, Yoburn BC. (1992). Potentiation of opioid analgesia by cocaine the role of spinal and supraspinal receptors. Life Sci. 50(8) 591-97. Smith FL, Cichewicz D, Martin ZL, Welch SP. (1998). The enhancement of morphine anti nociception in mice by delta9-tetrahydrocannabinol. Pharmacol Biochem Behav. 60(2) 559-66. 

Immune cells Opioid-binding sites have also been found on immune cells. The role of these receptors in nociception (response or sensitivity to painful stimuli) has not been determined. 

Taken together, these results show that the endocannabinoid system plays an important role in the physiological modulation of nociceptive transmission and in the development of inflammatory and neuropathic pain. Furthermore, the endocannabinoid system seems to participate in the antinociception induced by anti-inflammatory drugs, and displays an important synergic effect with opioid agonists. These data strongly support the therapeutic potential of cannabinoid receptor agonists for the treatment of chronic pain. 

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